The present invention is directed toward a pharmaceutical composition and a method of using the pharmaceutical composition to prevent and treat infections and diseases in mammals and avians.
The present invention relates to a method for preventing or treating infection and disease in a mammal or avian caused by a virus or other infective or disease agent. More specifically, the invention relates to the administration of a pharmaceutical composition to a mammal.
Viruses are associated with a large number of infections and diseases in avians and mammals, such as man. Although modern medical science has developed some treatment techniques that are effective to prevent a particular disease, e.g., the polio vaccine, the art generally lacks a method by which a large number of different virus infections can be effectively prevented or treated.
Past treatments of various diseases caused by viruses have been largely ineffective. Accordingly, there is a strong need for a method that can effectively treat or prevent infections and diseases caused by viruses in a mammal or avian. Although quaternary ammonium compounds have been known in the art, for example as described in U.S. Pat. No. 4,902,720, the contents of which are hereby incorporated by reference in their entirety, the art has failed to provide an effective treatment for a wide variety of infections and diseases associated with a variety of viruses, bacteria, fungi, and other disease causing agents. The present invention is addressed to this need.
A pharmaceutical composition is provided for systemically treating a living mammal or avian, comprising a first quaternary ammonium compound, a second quaternary ammonium compound and an organometallic compound in a vehicle suitable for systemically treating a living mammal or avian. A method of using the composition is also provided.
As used herein, when a preferred range such as 5-25 is given, this means preferably at least 5 and, separately and independently, preferably not more than 25. Parts are parts by weight and percentages are weight percent unless otherwise indicated or apparent.
The pharmaceutical composition comprises a quaternary ammonium compound (A) (sometimes referred to herein as Compound A), a quaternary ammonium compound (B) (sometimes referred to herein as Compound B), and an organometallic compound. The quaternary ammonium compound (A), the quaternary ammonium compound (B), and the organometallic compound (C) are preferably present in the pharmaceutical composition in a ratio relative to each other of 5 parts quaternary ammonium compound (A) to 5 parts quaternary ammonium compound (B) to 2 parts organometallic compound, less preferably as shown in the following formulation.
Preferably, quaternary ammonium compound (A) and quaternary ammonium compound (B) are present in the pharmaceutical composition in a ratio relative to each other of 1 part quaternary ammonium compound (A) to 1 part quaternary ammonium compound (B), less preferably 3 to 8 parts quaternary ammonium compound (A) to 2 to 7 parts quaternary ammonium compound (B), still less preferably 0.5 to 9.5 parts quaternary ammonium compound (A) to 0.5 to 9.5 parts quaternary ammonium compound 1 (B). Preferably, the quaternary ammonium compound (A) and organometallic compound are present in the pharmaceutical composition in a ratio relative to each other of 50 parts quaternary ammonium compound (A) to 2 parts organometallic compound, less preferably 25 to 75 parts quaternary ammonium compound (A) to 1 to 10 parts organometallic compound, still less preferably 10 to 100 parts quaternary ammonium compound (A) to 0.5 to 20 parts organometallic compound.
The pharmaceutical composition may be prepared in a stock solution using sterilized water. The table below sets forth a preferred formulation and less preferred formulations of the stock solution. All figures listed in the following table are in weight percent.
Alternatively the stock solution can be 5 g Compound A, 5 g Compound B, and 200 mg organometallic compound in 1 L sterile water.
Dilution of the stock solution creates a use solution. In the use solution, Compound A is preferably present at 0.5-0.00005 weight percent, more preferably 0.05-0.0005 weight percent, most preferably about 0.005 weight percent. Compound B is preferably present in the use solution at 0.5-0.00005 weight percent, more preferably 0.05-0.0005 weight percent, most preferably 0.005 weight percent. The use solution preferably contains 0.02-0.000002 weight percent of the organometallic compound, more preferably 0.002-0.00002 weight percent, most preferably 0.0002 weight percent.
The quaternary ammonium compound (A) is preferably a quaternary ammonium halide compound, more preferably an alkyl-dimethyl-benzyl-ammonium chloride. Still more preferably, the quaternary ammonium compound (A) is n-alkyl(60%C14, 30%C16, 5%C12, 5%C18)-dimethyl-benzyl-ammonium chloride.
The quaternary ammonium compound (B) is preferably a quaternary ammonium halide compound, more preferably an alkyl-dimethyl-ethylbenzyl-ammonium chloride. Still more preferably, the quaternary ammonium compound (B) is n-alkyl(68%C12, 32%C14)-dimethyl-ethylbenzyl-ammonium chloride.
The organo-metallic compound is preferably an organotin compound, more preferably a triorganotin compound. Still more preferably the organo-metallic compound is bis(tri-n-butyltin)oxide, or a water-soluble and/or water-dispersable ester of bis(tri-n-butyltin)oxide. Still more preferably, the organo-metallic compound is bis(tri-n-butyltin)oxide. Among the water-soluble and/or water dispersable esters of bis(tri-n-butyltin)oxide, tri-n-butyltin benzoate and tri-n-butyltin-butyrate are preferred.
Less preferably, the organo-metallic compound may be another organo-metallic compound, such as an organozinc compound, an organosilver compound, or an organogold compound.
A use solution of the pharmaceutical composition is prepared from the stock solution using a pharmaceutically effective carrier or diluent. The diluent may be lactated ringers, ringers, an NaCl solution, Normasol R, Normasol, or a 5% dextrose solution. The use solution is preferably prepared using a dilution ratio of diluent to stock solution of about 10,000:1 to 1:1, more preferably about 10,000:1 to 10:1, more preferably about 10,000:1 to 100:1, more preferably about 1,000:1 to 100:1, still more preferably about 1,000:1.
With a dilution ratio of 1,000:1 the pharmaceutical composition has a preferred formulation of 0.005% quaternary ammonium compound (A), 0.005% quaternary ammonium compound (B), and 0.002% (less preferably 0.0002%) organometallic compound.
The pharmaceutical composition is systemically administered to a mammal or avian infected with a virus. The mammals to which the pharmaceutical composition may be administered includes humans, equines, canines, felines, porcines, bovines, and other non-human mammals. The systemic administration of the pharmaceutical composition may be used to treat or prevent infections and diseases caused by viruses, bacteria, fungus and other microbes, and to treat or prevent the other diseases or conditions described herein.
The pharmaceutical composition may be systemically administered to a mammal or avian intravenously, subcutaneously, orally, intra-nasally, intramuscularly, or through nebulization.
The pharmaceutical composition can be administered to a mammal or avian in a dosage effective to produce an anti-viral effect with respect to the virus. The pharmaceutical composition can also be administered to a mammal or avian in a dosage effective to inhibit viral function of the virus. Of course, the same administration of the pharmaceutical composition to a mammal or avian can simultaneously achieve both of these effects.
The pharmaceutical composition can be administered in a therapeutically-effective dosage to the mammal or avian. Generally, the dosage of the pharmaceutical composition to be administered to a mammal or avian is 1 cc, less preferably 0.5-2 or 0.3-4 cc, of the pharmaceutical composition (with a stock dilution ratio of 1,000:1) per kilogram of the mammal or avian being treated over a 24 hour period, at a slow infusion rate. This dosage of the pharmaceutical composition is administered to the subject for a period of time generally lasting from 1 to 14 days.